RT Journal Article
SR Electronic
T1 Dual function of CTLA-4 in regulatory T cells and conventional T cells to prevent multiorgan autoimmunity
JF Proceedings of the National Academy of Sciences
JO Proc Natl Acad Sci USA
FD National Academy of Sciences
SP 1524
OP 1528
DO 10.1073/pnas.0910341107
VO 107
IS 4
A1 Jain, Nitya
A1 Nguyen, Hai
A1 Chambers, Cynthia
A1 Kang, Joonsoo
YR 2010
UL http://www.pnas.org/content/107/4/1524.abstract
AB Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an inhibitory receptor on T cells essential for maintaining T cell homeostasis and tolerance to self. Mice lacking CTLA-4 develop an early onset, fatal breakdown in T cell tolerance. Whether this autoimmune disease occurs because of the loss of CTLA-4 function in regulatory T cells, conventional T cells, or both is unclear. We show here that lack of CTLA-4 in regulatory T cells leads to aberrant activation and expansion of conventional T cells. However, CTLA-4 expression in conventional T cells prevents aberrantly activated T cells from infiltrating and fatally damaging nonlymphoid tissues. These results demonstrate that CTLA-4 has a dual function in maintaining T cell tolerance: CTLA-4 in regulatory T cells inhibits inappropriate naïve T cell activation and CTLA-4 in conventional T cells prevents the harmful accumulation of self-reactive pathogenic T cells in vital organs.